The purpose of this project is to define the humoral and cellular immune responses that relate to immunopathology, protective immunity and immunodiagnosis of patients with filariasis. To account for the marked quantitative differences in IgE production by patients with different clinical manifestations of filariasis, lymphocyte regulatory mechanisms have been studied. Blood mononuclear cells from helminth infected patients spontaneously produce abundant IgE in vitro in contrast to those from normals or atopic individuals; the mechanistic reasons for this are being examined. A filarial antigen specific T-cell line and clones have been developed and utilized to show that antigen presentation is genetically controlled (DR-restricted) and that factors mediating B-cell activation to produce IgE can be identical and distinguished from those leading to production of other immunoglobulins. Use of sensitive qualitative techniques (immunoblotting) to analyze IgE antibodies in infected patients has revealed differences in allergen recognition unappreciated in prior studies. The presence of IgG blocking antibodies that inhibit immediate hypersensitivity responses to parasite antigen correlates with clinical findings in infected patients and, thus, may have pathogenetic significance. Analysis of IgG subclasses has shown extreme elevations of IgG4 antibody in the response to infection. Furthermore, there is profound qualitative similarity between IgE and IgG4 responses to parasite antigens; the possibility that IgG4 is the blocking antibody is being investigated. Identification of filarial antigens in the circulation of patients has been successful using a 2-site immunoradiometric assay and immunoblotting. A single, specific heat-stable glycoprotein of 200 kd m.w. can be identified in all microfilaremic patients with W. bancrofti filariasis and some without microfilaremia. Isolation of the antigen and production of monoclonal antibodies to it are underway.